Considerable progress has been made in elucidating the neural pathways underlying conditioned fear in animals. This work has implicated circuits centered around the amygdala, and interactions between the amygdala, hippocampus and medial frontal cortex (mPFC), in the acquisition and/or expression of different aspects of conditioned fear. Research in humans has confirmed essential aspects of the animal work. Further, the same trio of brain regions (amygdala, hippocampus, mPFC) are also implicated in the regulation of stress hormones and are also often altered in patients with fear/anxiety disorders. The overall hypothesis guiding research in the Center for the Neuroscience of Fear and Anxiety (CNFA) is that the effects of stress on fear circuits in animals mimics changes that occur in the brains of patients with fear-related disorders relative to healthy controls. To test and explore the implications of this hypothesis, we use the same behavioral paradigm, fear conditioning, to study rats, normal humans, and patients with fear disorders. The aim of the animal work is to examine the effects of stress on the behavioral functions, physiology, and morphology of fear circuits. The aim of the studies of normal humans is to use behavioral methods and fMRI to extend our understanding of fear mechanisms in the human brain and to develop new probes for testing patients with fear disorders. And the aim of the studies of patients with fear disorders is to determine whether the patterns of functional brain activation during fear in healthy humans are altered in patients with fear disorders, and whether these alterations are consistent with the effects of stress on fear circuits, as determined in the animal work. In pursuing these goals, several new themes will also be pursued across the various projects, including an emphasis on questions about circuit interactions in fear, the role of individual and sex differences, and treatment related issues. Through this translational research we hope to reveal brain mechanisms that are altered in patients with fear/anxiety disorders and, in the long run, to identify new hypotheses about how to treat or prevent such disorders.